Development of the normal sexual dimorphisms of several mammals (rats, rabbits, dogs, cattle, monkeys) apparently depends upon pre- or perinatal exposure to androgens. Male-directed differentiation of the reproductive tract, the neuro-endocrine system (mating behavior and gonadotrophin secretion), and the liver (steroid-metabolizing enzymes) appears to be mediated by the testis in rats late during pregnancy and in early neonatal life. This metabolic sexual dimorphism of rat liver (sex-specific metabolism of steroids) exists in the absence of plasma steroid binding protein in adults of this species, in contrast to other mammals studied in which hepatic steroid metabolic rates in vitro are the same in both sexes, but in which plasma concentrations of sex steroid binding protein are sex-specific (greater in females). This proposal will examine the hypothesis that the plasma sex-steroid binding protein (SBP) represents a functional extension of the liver, regulating the peripheral metabolism of plasma androgens, thereby obviating the need for an intrinsic hepatic regulatory system. We propose that SBP and steroid-metabolising enzymes in target tissues are differentiated simultaneously with the liver and the neuro-endocrine system under the control of 'prenatal' androgens. Plasma SBP concentrations, metabolic clearance rates (MCR's) of dehydroepiandrosterone (low binding affinity) and testosterone (high binding affinity), and the hepatic and skin metabolism in vitro of these androgens will be evaluuted in normal and pseudohermaphroditic rats, rabbits and rhesus monkeys.